Many emerging infectious diseases are caused by single strand RNA viruses. The major outbreaks of dengue fever, West Nile encephalitis, Chikungunya fever, and Rift Valley fever that have occurred in recent decades, each with a significant impact on human health, highlight the urgent need to understand the factors that allow these viruses to invade new territories or adapt to new host or vector species.
These events are often perceived as a warning signs for a potential pandemic. In the case of pandemic, understanding the factors that shape the adaptability of these rapidly evolving infectious agents and our ability to promptly develop a vaccine will be the critical steps for controlling the spread of the disease.
Indeed, to this date, vaccination still remains the best approach for reducing mortality and morbidity of humans caused by such viruses. In particular, live attenuated vaccines are highly successful due to stimulation of different arms of the host immune response. These live attenuated vaccines are natural virus variants derived by passaging virus in abnormal hosts. However, the preparation of a live attenuated vaccine suffers from many drawbacks, especially since its preparation relies on an empirical and time-consuming method. Therefore, it currently takes a long time to develop a useful vaccine that can be administered to humans.
There is thus an unmet need for an approach of generating attenuated viruses, that has no possibility of reversion and that provides a fast, efficient, cost-effective and safe method of manufacturing a vaccine candidate.
The present invention fulfills this need by providing a systematic approach for designing future vaccine candidates that have essentially no possibility of reversion. This method is broadly applicable to a wide range of viruses and provides an effective approach for producing a wide variety of anti-viral vaccines.